1. “MECHANISM OF CELL REGENERATION”
FARKHANDA GUL
M.Phil 1ST SEM

2. Contents
 Introduction
 Mechanisms of Differentiation
 Aspects relating to stem cells
 Control of gene expression
 Influence of the extracellular matrix and cell-cell interaction
 Regeneration in different animals
 Response to injury
 Tissue regeneration
 Conclusion

3. OBJECTIVE

4. INTRODUCTION
Involves the capacity for renewal or recomposition
Tissues, organs or even organisms
Injury or damage
 Resulting from pathologies, tumors, congenital diseases
or traumas (Sephel &Woodward, 2011).

5. Both the composition and the tissue properties are restored
Newly formed tissue is highly similar to the original tissue
Capable of proliferation and differentiation
By intense production of extracellular matrix, with large
amounts of collagen. (Hoffmann & Tsonis, 2013).

6. Fig 01: Extracellular matrix of bone (Organ repair and regeneration,2012)

7. Mechanisms of Differentiation
 Zygote, classified as totipotent, has the potential to originate any type of
cell, among more than two hundred cell types.
 The cells gradually exhibit changes in the gene expression pattern.
 In this stage the morphogens, soluble inductive factors, play a vital role in
cell differentiation
 Resulting in the development of a specific type of cell, i.e., cell
differentiation.
 The differentiated cells keep the gene expression pattern stable, allowing
the expression of its characteristic phenotype (Robey; 2000).

8. Aspects relating to stem cells
Unspecialized cells
Having capacity to differentiate into any types of cells.
In the adult organism the
Stem cells, called somatic, maintain the self-renewal capacity

9. Stem cells found in:
Fig 02: S tem cells in different organs (Tissue engineering and regenerative medicine,2010)

10. Deterministic and Stochastic Models
Deterministic
division of a stem cell
produces another stem
cell
ability to
differentiate/progenitor
cell
Stochastic
some stem cells generate
only stem cells
while others generate
differentiated cells
Maintained in the adult organism by two main mechanisms (Levine &
Tijan, 2003).

11.  In adult organisms the stem cells diminish over time, and older individuals
have a smaller amount of stem cells
 With aging, mechanisms such as cell senescence and apoptosis are
apparently related to a decrease in the proliferative capacity of stem cells,
 resulting from the accumulation of intrinsic (DNA mutations) and extrinsic
factors (changes in the microenvironment of stem cells)
 factors (both internal and external), or mediators, are essential for the
maintenance of these cells
 Can lead activation of the stem cells (Paunesku; 2001).

12. FACTORS IN ACTIVATION OF STEM CELLS
factors originating
from
distant sources

13. Inhibition of cyclin CDK
 Cdks signal the cell that it is ready to pass into the next stage of the cell
cycle.
 There are some inhibitory proteins which blocks the cell cycle
 In case of any damage or injury to cell
 protein p53 is one of those responsible for blocking the cell cycle,
especially in the presence of DNA damage.
 The increase in protein p53 induces the expression of p21 protein, which in
 turn binds, through the amino-terminal region, to the cyclin-CDK (cyclin-
dependent kinase)
 complex, usually responsible for cell cycle progression.

14. Control of gene expression
 Certain genes are expressed throughout cell differentiation,
 Gene expression takes place in transcription
 Transcription factors are proteins that bind specifically to
 DNA sequences, inducing or repressing gene expression,
 The transcription factors act specifically at DNA sites, more specifically the
following sequences: promoters, or binding sites for the
 RNA polymerase; enhancers and silencers,
 Changes caused by methylation in general hinder gene expression (Torres &

15. Influence of the extracellular matrix and cell-cell
interaction
 The ECM can be defined as an interconnected network of
macromolecules composed of
 Adhesive proteins, structural fibrous proteins (collagen and elastin),
glycoproteins and specialized proteins (such as growth factors).
 The influence of the extracellular matrix (ECM) in the
differentiation process involves the presence of factors immobilized
in the ECM

16. Dedifferentiation
 Involves undifferentiated cells returning to a less differentiated phase of its own
lineage.
 Dedifferentiation, cellular process in which undifferentiated cell reverts to
an earlier developmental stage, usually as part of a regenerative process.
 This process allows the cell to proliferate again before redifferentiation, which
leads to the substitution of these cells that were lost.

17. Fig 03: Differentiation in muscle cells (The cellular basis for animal regeneration, 2011)

18. Trans differentiation
 Another natural mechanism that was observed for the first time in
the regeneration of the salamander lens over 100 years ago.
Trans differentiation, is a process where one mature somatic
cell transforms into another mature somatic cell.
 Involves the conversion of a differentiated cell type into another cell
type

19. Fig 04: Transdifferentiation (Principles of tissue regeneration, 2013)

20. Reprogramming
 Differentiate into almost any type of cell.
 Although reprogramming occurs naturally during fertilization to produce
totipotent cells that can differentiate into any type of cell

21. Fig 05: Reprogramming of cells (Principles of tissue regeneration, 2013)

22. Regeneration in different animals
 Some animals, such as starfish, planaria (flatworms) and Hydra have
significant regenerative capacity, and can originate complete specimens from
small fragments (Torres & Parfitt, 2007).

23. ZEBRAFISH
 Fins and tail of zebrafish can regenerate.
 This fish can also regenerate cardiac tissue after resection or the destruction of
cardiomyocyte's. (Santos, Wada, Carvalho; 2013).

24. Fig 06: Regeneration in fish (Cellular and molecular biology, 2013)

25. Hydra
 When cross sectioned, Hydra will regenerate
 the sectioning surface closest to the head forms a head. The same applies to the
foot.

26. Fig 07: Regeneration in fish (Cellular and molecular biology, 2013)

27. Response to injury
 The regenerative response is initiated through recognition of the loss
of tissue or local wound.
 Which influence the activation of many processes for regeneration

28. Formation of the scar epithelium on wounds
 It is an early response to the injury and consists of the migration of
epithelial cells to the tissue lesion (Schwank; 2002).
 The wound epithelium plays an important role in subsequent
regeneration events.
 The formation of this wound epithelium is a target for a variety of
regulatory events (Levine & Tijan, 2003).

29. Tissue regeneration
 Another type of regeneration that involves proliferation, close to the cut
surface
 It involves the restoration of tissues damaged
 Classical examples of this type of regeneration in mammals are the skin,
bones and regeneration of the skeletal muscle (Torres & Parfitt, 2007).

30. Conclusion
 The goal of regenerative medicine is to restore the cells, tissues and
structures that are lost or damaged after disease, injury or aging.
 It is necessary to get a better idea of the cell differentiation, trans
differentiation, dedifferentiation and redifferentiation mechanisms that
occur in different contexts, such as during regeneration in animals.
 The participation of stem cells and progenitor cells in this process is also
of considerable relevance.
 The understanding of these mechanisms can facilitate highly relevant
therapeutic strategies in regenerative medicine and tissue engineering.

31. References
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